Recent genomic breakthroughs have revolutionized our understanding of cancer. It is now possible to envision treatment paradigms that would be individualized, targeted and tailored according to the tumor genetic profile. However, high-throughput functional assays capable of identifying and validating potential cancer drugs, based on abnormal tumor gene expression profiles, in a setting that would directly translate to providing recommendations for patient treatment are not readily available. The human tumor stem cell assay (HTSCA), also known as anchorage-independent growth assay, has been considered as the "gold standard" for chemosensitivity testing of patient tumor cells. In its current format, the HTSCA suffers from many pitfalls that make it unfit for high-throughput clinical testing. Falcon Genomics, Inc. is developing the Cancer BioChip System (CBCS), a rapid, high-throughput, automated, and quantitative anchorage-independent growth assay for the personalized identification and validation of inhibitors of cancer cell growth. We will use silencing RNA (siRNA) or short hairpin RNA (shRNA) to inhibit expression of abnormally expressed tumor genes and test their impact on anchorage-independent tumor growth in a high-throughput fashion. In this Phase I application, we will develop a Test Cancer BioChip for optimizing plating, transfection, silencing, and cytostatic efficiencies. Results from these studies will validate the CBCS as a tool for cancer target identification and validation. Through future clinical trials, we anticipate development of the CBCS into a cancer diagnostic and personalized therapeutic tool. PUBLIC HEALTH RELEVANCE: This Phase-1 grant application is relevant to the mission of the National Institute of Health since it will provide for a Cancer BioChip System that will assist in the diagnosis and development of cancer therapies. It will initially offer a novel personalized approach to the evaluation and treatment of breast cancer patients. However, it is not limited to breast cancer since all types of cancers that are capable of growing in an anchorage-independent fashion can be tested on the Cancer BioChip System.